DESCRIPTION: There are 5 specific aims for this proposal. 1. To identify the gene affected by the Cle mutation. This is likely (but not 100% certain) to be a mutation in the Pax6 gene. Pax6 will be PCR amplified and sequenced. If not amplifiable, RFLP analysis will determine if the gene has been deleted. If these are both negative, then a limited search for a mutation in the regulatory region of Pax6 is proposed. 2. The mutants Tcm, Cat4a and Coc will be characterized. The first two by positional candidate strategy. If unsuccessful, then by positional cloning strategies. For Coc, mouse ys crystallin will first be cloned and mapped. If near Coc, the ys from Coc will be sequenced and compared to normal. 3. Hfi has been shown to be a mutation in the lens membrane protein MIP. This specific aim will characterize the effect of the Mip mutation on RNA expression and protein production in the Hfi mutant. The expression of MIP will be examined using Northern analysis, in situ hybridization, and immunohistochemistry. Mutant MIP will be expressed in Xenopus oocytes. 4. 8 new mouse autosomal dominant cataract mutations will be mapped. Crosses will generate F1 hybrids and backcross progeny, in which microsatellite markers will be screened. 5. The four most interesting mutations based on phenotype and unique location on the mouse chromosome in specific aim #4 will be selected and the developmental histopathology studied.